Department / Division Affiliations
|Professor, Molecular & Medical Pharmacology|
|Member, CTSI, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, JCCC Cancer Molecular Imaging, Molecular Pharmacology GPB Home Area, Physics & Biology in Medicine GPB Home Area|
Dr. Radu’s lab aims to develop a pipeline of novel therapeutics and companion diagnostics for cancer and other disorders that impact public health. The group focuses on the metabolic pathways involved in nucleotide biosynthesis. Fundamental cellular processes such as cell division, DNA repair and viral infection increase the demand for nucleotides. Alterations in nucleotide metabolism occur in various disease states, including cancer, immune disorders and infection. The lab’s research program leverages three key components, with which the group has extensive expertise: 1) unique in vitro and in vivo experimental models, 2) development of new biomarkers for measuring nucleotide metabolism in vitro and in vivo, using platforms such as Positron Emission Tomography (PET) and mass spectrometry, 3) drug discovery and development. By integrating these three components into an interdisciplinary approach referred to as the “Triangle concept” and through extensive collaborations with colleagues at UCLA and investigators at other institutions the group has recently developed a new therapeutic approach to interfere with nucleotide metabolism in acute lymphoblastic leukemia. The ‘biology of disease’ component of this example of a Triangle-based approach concerned the use of new mouse genetic models to study two biochemical pathways that converge on the synthesis of deoxyribonucleotide triphosphate (dNTP) precursors for DNA replication. The ‘therapeutics’ component concerned the development of small molecule inhibitors of deoxycytidine kinase (dCK), a key enzyme in dNTP biosynthesis. The ‘molecular diagnostics’ component concerned the development of a clinically applicable companion pharmacodynamic imaging method, using PET imaging. With this assay, investigators can non-invasively monitor dCK activity in vivo and thus the efficacy of pharmacological interventions that target this kinase. Ongoing translational projects in the lab are applying the Triangle concept to additional cancers and immune disorders, as well as to developmental processes such as hematopoiesis, cellular reprogramming and pluripotency.
Nathanson David A, Armijo Amanda L, Tom Michelle, Li Zheng, Dimitrova Elizabeth, Austin Wayne R, Nomme Julian, Campbell Dean O, Ta Lisa, Le Thuc M, Lee Jason T, Darvish Ryan, Gordin Ari, Wei Liu, Liao Hsiang-I, Wilks Moses, Martin Colette, Sadeghi Saman, Murphy Jennifer M, Boulos Nidal, Phelps Michael E, Faull Kym F, Herschman Harvey R, Jung Michael E, Czernin Johannes, Lavie Arnon, Radu Caius G Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication. The Journal of experimental medicine. 2014; .
Nomme Julian, Murphy Jennifer M, Su Ying, Sansone Natasha D, Armijo Amanda L, Olson Steven T, Radu Caius, Lavie Arnon Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules. Acta crystallographica. Section D, Biological crystallography. 2014; 70(Pt 1): 68-78.
Wang Jun, Hwang Kiwook, Braas Daniel, Dooraghi Alex, Nathanson David, Campbell Dean O, Gu Yuchao, Sandberg Troy, Mischel Paul, Radu Caius, Chatziioannou Arion F, Phelps Michael E, Christofk Heather, Heath James R Fast metabolic response to drug intervention through analysis on a miniaturized, highly integrated molecular imaging system. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2013; 54(10): 1820-4.
Gil Jose S, Machado Hidevaldo B, Campbell Dean O, McCracken Melissa, Radu Caius, Witte Owen N, Herschman Harvey R Application of a Rapid, Simple, and Accurate Adenovirus-Based Method to Compare PET Reporter Gene/PET Reporter Probe Systems. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 2013; 15(3): 273-81.
Herrmann Ken, Dahlbom Magnus, Nathanson David, Wei Liu, Radu Caius, Chatziioannou Arion, Czernin Johannes Evaluation of the Genisys4, a Bench-Top Preclinical PET Scanner. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2013; 15(3): .
Austin Wayne R, Armijo Amanda L, Campbell Dean O, Singh Arun S, Hsieh Terry, Nathanson David, Herschman Harvey R, Phelps Michael E, Witte Owen N, Czernin Johannes, Radu Caius G Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide metabolism with replication stress. The Journal of experimental medicine. 2012; 209(12): 2215-28.
Aarntzen Erik H J G, Srinivas Mangala, Radu Caius G, Punt Cornelis J A, Boerman Otto C, Figdor Carl G, Oyen Wim J G, de Vries I Jolanda M In vivo imaging of therapy-induced anti-cancer immune responses in humans. Cellular and molecular life sciences : CMLS. 2012; 209(12): .
Benz Matthias R, Czernin Johannes, Allen-Auerbach Martin S, Dry Sarah M, Sutthiruangwong Piriya, Spick Claudio, Radu Caius, Weber Wolfgang A, Tap William D, Eilber Fritz C 3'-deoxy-3'-[(18) F]fluorothymidine positron emission tomography for response assessment in soft tissue sarcoma: A pilot study to correlate imaging findings with tissue thymidine kinase 1 and Ki-67 activity and histopathologic response. Cancer. 2012; 118(12): 3135-44.
Vatakis Dimitrios N, Bristol Gregory C, Kim Sohn G, Levin Bernard, Liu Wei, Radu Caius G, Kitchen Scott G, Zack Jerome A Using the BLT humanized mouse as a stem cell based gene therapy tumor model. Journal of visualized experiments : JoVE. 2012; 15(70): e4181.
Lee Jason T, Campbell Dean O, Satyamurthy Nagichettiar, Czernin Johannes, Radu Caius G Stratification of nucleoside analog chemotherapy using 1-(2'-deoxy-2'-18F-fluoro-Î˛-D-arabinofuranosyl)cytosine and 1-(2'-deoxy-2'-18F-fluoro-Î˛-L-arabinofuranosyl)-5-methylcytosine PET. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2012; 53(2): 275-80.
Yaghoubi Shahriar S, Campbell Dean O, Radu Caius G, Czernin Johannes Positron emission tomography reporter genes and reporter probes: gene and cell therapy applications. Theranostics. 2012; 2(4): 374-91.
Campbell Dean O, Yaghoubi Shahriar S, Su Ying, Lee Jason T, Auerbach Martin S, Herschman Harvey, Satyamurthy Nagichettiar, Czernin Johannes, Lavie Arnon, Radu Caius G Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe. The Journal of biological chemistry. 2012; 287(1): 446-54.
Vatakis Dimitrios N, Koya Richard C, Nixon Christopher C, Wei Liu, Kim Sohn G, Avancena Patricia, Bristol Gregory, Baltimore David, Kohn Donald B, Ribas Antoni, Radu Caius G, Galic Zoran, Zack Jerome A Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108(51): E1408-16.
Ma Chao, Fan Rong, Ahmad Habib, Shi Qihui, Comin-Anduix Begonya, Chodon Thinle, Koya Richard C, Liu Chao-Chao, Kwong Gabriel A, Radu Caius G, Ribas Antoni, Heath James R A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells. Nature medicine. 2011; 17(6): 738-43.
Ng Quinn K T, Su Helen, Armijo Amanda Lee, Czernin Johannes, Radu Caius G, Segura Tatiana Clustered Arg-Gly-Asp peptides enhances tumor targeting of nonviral vectors. ChemMedChem. 2011; 6(4): 623-7.
Schwarzenberg Johannes, Radu Caius G, Benz Matthias, Fueger Barbara, Tran Andrew Q, Phelps Michael E, Witte Owen N, Satyamurthy Nagichettiar, Czernin Johannes, Schiepers Christiaan Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway. European journal of nuclear medicine and molecular imaging. 2011; 38(4): 711-21.
Zheng Xiujuan, Yu Chin-Lung, Sha Wei, Radu Caius, Huang Sung-Cheng, Feng Dagan Study of an image-derived SUV and a modified SUV using mouse FDG-PET. Nuclear medicine and biology. 2011; 38(3): 353-62.
Rabinovich Brian A, Radu Caius G Imaging adoptive cell transfer based cancer immunotherapy. Current pharmaceutical biotechnology. 2010; 11(6): 672-84.
Koya Richard C, Mok Stephen, Comin-Anduix BegoĂ±a, Chodon Thinle, Radu Caius G, Nishimura Michael I, Witte Owen N, Ribas Antoni Kinetic phases of distribution and tumor targeting by T cell receptor engineered lymphocytes inducing robust antitumor responses. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(32): 14286-91.
Shu Chengyi J, Campbell Dean O, Lee Jason T, Tran Andrew Q, Wengrod Jordan C, Witte Owen N, Phelps Michael E, Satyamurthy Nagichettiar, Czernin Johannes, Radu Caius G Novel PET probes specific for deoxycytidine kinase. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2010; 51(7): 1092-8.
Nair-Gill Evan, Wiltzius Stephanie M, Wei Xiao X, Cheng Donghui, Riedinger Mireille, Radu Caius G, Witte Owen N PET probes for distinct metabolic pathways have different cell specificities during immune responses in mice. The Journal of clinical investigation. 2010; 120(6): 2005-15.
Brewer Sarah, Nair-Gill Evan, Wei Bo, Chen Ling, Li Xiaoxiao, Riedinger Mireille, Campbell Dean O, Wiltzius Stephanie, Satyamurthy Nagichettiar, Phelps Michael E, Radu Caius, Witte Owen N, Braun Jonathan Epithelial uptake of [18F]1-(2'-deoxy-2'-arabinofuranosyl) cytosine indicates intestinal inflammation in mice. Gastroenterology. 2010; 138(4): 1266-75.
Ribas Antoni, Benz Matthias R, Allen-Auerbach Martin S, Radu Caius, Chmielowski Bartosz, Seja Elizabeth, Williams John L, Gomez-Navarro Jesus, McCarthy Timothy, Czernin Johannes Imaging of CTLA4 blockade-induced cell replication with (18)F-FLT PET in patients with advanced melanoma treated with tremelimumab. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2010; 51(3): 340-6.
Toy Gerald, Austin Wayne R, Liao Hsiang-I, Cheng Donghui, Singh Arun, Campbell Dean O, Ishikawa Tomo-o, Lehmann Lynn W, Satyamurthy Nagichettiar, Phelps Michael E, Herschman Harvey R, Czernin Johannes, Witte Owen N, Radu Caius G Requirement for deoxycytidine kinase in T and B lymphocyte development. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(12): 5551-6.
Mikkola Hanna K A, Radu Caius G, Witte Owen N Targeting leukemia stem cells. Nature biotechnology. 2010; 28(3): 237-8.
Laing Rachel E, Nair-Gill Evan, Witte Owen N, Radu Caius G Visualizing cancer and immune cell function with metabolic positron emission tomography. Current opinion in genetics & development. 2010; 20(1): 100-5.
Guo Deliang, Cloughesy Timothy F, Radu Caius G, Mischel Paul S AMPK: A metabolic checkpoint that regulates the growth of EGFR activated glioblastomas. Cell cycle (Georgetown, Tex.). 2010; 9(2): 211-2.
Kottyan Leah C, Collier Ann R, Cao Khanh H, Niese Kathryn A, Hedgebeth Megan, Radu Caius G, Witte Owen N, Khurana Hershey Gurjit K, Rothenberg Marc E, Zimmermann Nives Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner. Blood. 2009; 114(13): 2774-82.
Guo Deliang, Hildebrandt Isabel J, Prins Robert M, Soto Horacio, Mazzotta Mary M, Dang Julie, Czernin Johannes, Shyy John Y-J, Watson Andrew D, Phelps Michael, Radu Caius G, Cloughesy Timothy F, Mischel Paul S The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(31): 12932-7.
Kwong Gabriel A, Radu Caius G, Hwang Kiwook, Shu Chengyi J, Ma Chao, Koya Richard C, Comin-Anduix Begonya, Hadrup Sine Reker, Bailey Ryan C, Witte Owen N, Schumacher Ton N, Ribas Antoni, Heath James R Modular nucleic acid assembled p/MHC microarrays for multiplexed sorting of antigen-specific T cells. Journal of the American Chemical Society. 2009; 131(28): 9695-703.
Wang Hao, Wang Shutao, Su Helen, Chen Kuan-Ju, Armijo Amanda Lee, Lin Wei-Yu, Wang Yanju, Sun Jing, Kamei Ken-ichiro, Czernin Johannes, Radu Caius G, Tseng Hsian-Rong A supramolecular approach for preparation of size-controlled nanoparticles. Angewandte Chemie (International ed. in English). 2009; 48(24): 4344-8.
Yu Zeta Tak For, Kamei Ken-ichiro, Takahashi Hiroko, Shu Chengyi Jenny, Wang Xiaopu, He George Wenfu, Silverman Robert, Radu Caius G, Witte Owen N, Lee Ki-Bum, Tseng Hsian-Rong Integrated microfluidic devices for combinatorial cell-based assays. Biomedical microdevices. 2009; 11(3): 547-55.
Laing Rachel E, Walter Martin A, Campbell Dean O, Herschman Harvey R, Satyamurthy Nagichettiar, Phelps Michael E, Czernin Johannes, Witte Owen N, Radu Caius G Noninvasive prediction of tumor responses to gemcitabine using positron emission tomography. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(8): 2847-52.
Shu Chengyi J, Radu Caius G, Shelly Stephanie M, Vo Dan D, Prins Robert, Ribas Antoni, Phelps Michael E, Witte Owen N Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen. International immunology. 2009; 21(2): 155-65.
Wei Liu H, Olafsen Tove, Radu Caius, Hildebrandt Isabel J, McCoy Mark R, Phelps Michael E, Meares Claude, Wu Anna M, Czernin Johannes, Weber Wolfgang A Engineered antibody fragments with infinite affinity as reporter genes for PET imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2008; 49(11): 1828-35.
Prins Robert M, Shu Chengyi J, Radu Caius G, Vo Dan D, Khan-Farooqi Haumith, Soto Horacio, Yang Meng-Yin, Lin Muh-Shi, Shelly Stephanie, Witte Owen N, Ribas Antoni, Liau Linda M Anti-tumor activity and trafficking of self, tumor-specific T cells against tumors located in the brain. Cancer immunology, immunotherapy : CII. 2008; 57(9): 1279-89.
Radu Caius G, Shu Chengyi J, Nair-Gill Evan, Shelly Stephanie M, Barrio Jorge R, Satyamurthy Nagichettiar, Phelps Michael E, Witte Owen N Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog. Nature medicine. 2008; 14(7): 783-8.
Tumeh Paul C, Radu Caius G, Ribas Antoni PET imaging of cancer immunotherapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2008; 49(6): 865-8.
Peter Christoph, Waibel Michaela, Radu Caius G, Yang Li V, Witte Owen N, Schulze-Osthoff Klaus, Wesselborg Sebastian, Lauber Kirsten Migration to apoptotic "find-me" signals is mediated via the phagocyte receptor G2A. The Journal of biological chemistry. 2008; 283(9): 5296-305.
Nair-Gill Evan D, Shu Chengyi J, Radu Caius G, Witte Owen N Non-invasive imaging of adaptive immunity using positron emission tomography. Immunological reviews. 2008; 221(9): 214-28.
McLaughlin Jami, Cheng Donghui, Singer Oded, Lukacs Rita U, Radu Caius G, Verma Inder M, Witte Owen N Sustained suppression of Bcr-Abl-driven lymphoid leukemia by microRNA mimics. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(51): 20501-6.
Huang Julie H, CĂˇrdenas-Navia L Isabel, Caldwell Charles C, Plumb Troy J, Radu Caius G, Rocha Paulo N, Wilder Tuere, Bromberg Jonathan S, Cronstein Bruce N, Sitkovsky Michail, Dewhirst Mark W, Dustin Michael L Requirements for T lymphocyte migration in explanted lymph nodes. Journal of immunology (Baltimore, Md. : 1950). 2007; 178(12): 7747-55.
Bailey Ryan C, Kwong Gabriel A, Radu Caius G, Witte Owen N, Heath James R DNA-encoded antibody libraries: a unified platform for multiplexed cell sorting and detection of genes and proteins. Journal of the American Chemical Society. 2007; 129(7): 1959-67.
Radu Caius G, Shu Chengyi J, Shelly Stephanie M, Phelps Michael E, Witte Owen N Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(6): 1937-42.
Yang Li V, Radu Caius G, Roy Meenakshi, Lee Sunyoung, McLaughlin Jami, Teitell Michael A, Iruela-Arispe M Luisa, Witte Owen N Vascular abnormalities in mice deficient for the G protein-coupled receptor GPR4 that functions as a pH sensor. Molecular and cellular biology. 2007; 27(4): 1334-47.
Radu Caius G, Cheng Donghui, Nijagal Amar, Riedinger Mireille, McLaughlin Jami, Yang Li V, Johnson James, Witte Owen N Normal immune development and glucocorticoid-induced thymocyte apoptosis in mice deficient for the T-cell death-associated gene 8 receptor. Molecular and cellular biology. 2006; 26(2): 668-77.
Shu Chengyi J, Guo Shuling, Kim Young J, Shelly Stephanie M, Nijagal Amar, Ray Pritha, Gambhir Sanjiv S, Radu Caius G, Witte Owen N Visualization of a primary anti-tumor immune response by positron emission tomography. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(48): 17412-7.
Wang Li, Radu Caius G, Yang Li V, Bentolila Laurent A, Riedinger Mireille, Witte Owen N Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A. Molecular biology of the cell. 2005; 16(5): 2234-47.
Radu Caius G, Nijagal Amar, McLaughlin Jami, Wang Li, Witte Owen N Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(5): 1632-7.
Yang Li V, Radu Caius G, Wang Li, Riedinger Mireille, Witte Owen N Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A. Blood. 2005; 105(3): 1127-34.
Radu Caius G, Yang Li V, Riedinger Mireille, Au Matthew, Witte Owen N T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101(1): 245-50.
Deng Caishu, Radu Caius, Diab Asim, Tsen May F, Hussain Rehana, Cowdery John S, Racke Michael K, Thomas James A IL-1 receptor-associated kinase 1 regulates susceptibility to organ-specific autoimmunity. Journal of immunology (Baltimore, Md. : 1950). 2003; 170(6): 2833-42.
He Xiao-lin, Radu Caius, Sidney John, Sette Alessandro, Ward E Sally, Garcia K Christopher Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au. Immunity. 2002; 17(1): 83-94.